# Role of hydroxychloroquine in primary glomerular disease - a systematic review and meta-analysis of the current evidence

**Authors:** Gerry George Mathew, Shanmugam Sundaramurthy, Prakash Muthuperumal, V. Jayaprakash

PMC · DOI: 10.1186/s12882-025-04370-2 · 2025-08-04

## TL;DR

This review evaluates how hydroxychloroquine affects kidney disease by reducing proteinuria and its safety profile.

## Contribution

The study provides a systematic review and meta-analysis of hydroxychloroquine's effects on primary glomerular diseases.

## Key findings

- Hydroxychloroquine significantly reduced proteinuria, especially in membranous nephropathy and with longer treatment.
- No significant improvement in eGFR was observed after hydroxychloroquine treatment.
- Common adverse events included gastrointestinal and mucocutaneous effects.

## Abstract

Hydroxychloroquine is increasingly being used to treat primary glomerular diseases. It has shown promising results in terms of reducing proteinuria and stabilizing kidney function. This systematic review aimed to assess the effects of HCQ on proteinuria and the estimated glomerular filtration rate (eGFR) in primary glomerular diseases and evaluate its safety profile.

A literature search was conducted using PubMed, ScienceDirect, Springer, and Google Scholar for articles published between 2014 and 2024. Articles incorporating hydroxychloroquine for the treatment of primary glomerular diseases were considered. These studies evaluated the effect of HCQ on 24-hour proteinuria and eGFR. Pooled mean differences (MDs) and heterogeneity metrics (Tau², I², and Q-test) were analysed. The safety data from all included studies were reviewed.

HCQ administration significantly reduced proteinuria (MD = -0.69, 95% CI= -0.79 to -0.59), with pronounced effects for longer treatment durations (MD = -0.74, 95% CI= -0.81 to -0.67), and in patients with membranous nephropathy (MD = -3.00, 95% CI= -4.46 to -1.53). Conversely, no significant improvement in eGFR was observed after HCQ treatment (MD = -1.03, 95% CI= -2.73 to − 0.67). A beneficial effect was noticed in patients with IgA nephropathy (MD = -2.65, 95% CI= -5.16 to -0.14). Moderate to substantial heterogeneity (I² = 69–95%) was observed for proteinuria outcomes, but no heterogeneity was found for eGFR outcomes (I² = 0%). 69 adverse events were reported, of which gastrointestinal and mucocutaneous effects were the most common.

HCQ therapy for primary glomerular diseases showed a trend toward reducing proteinuria without significant effects on eGFR, with a better safety profile.

This systematic review was registered in PROSPERO with ID CRD42024597762.

## Linked entities

- **Chemicals:** hydroxychloroquine (PubChem CID 3652)
- **Diseases:** membranous nephropathy (MONDO:0005376), IgA nephropathy (MONDO:0005342)

## Full-text entities

- **Genes:** ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, PLA2R1 (phospholipase A2 receptor 1) [NCBI Gene 22925] {aka CLEC13C, PLA2-R, PLA2G1R, PLA2IR, PLA2R}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}
- **Diseases:** rheumatological disorders (MESH:D012216), Proteinuria (MESH:D011507), IgA glomerulonephritis (MESH:D017098), diabetic nephropathy (MESH:D003928), cardiovascular complications (MESH:D002318), MN (MESH:D015433), pruritus (MESH:D011537), faecal occult blood (MESH:D005596), hypersensitivity (MESH:D004342), SLE (MESH:D008180), infection (MESH:D007239), liver dysfunction (MESH:D017093), inflammation (MESH:D007249), renal failure (MESH:D051437), ESRD (MESH:D007676), malignancies (MESH:D009369), cerebrovascular accidents (MESH:D020521), skin pigmentation (MESH:D010859), inflammatory cytokines (MESH:D000080424), constipation (MESH:D003248), alopecia (MESH:D000505), MCD (MESH:D009402), MPGN (MESH:D015432), diarrhoea (MESH:D003967), primary (MESH:D010538), retinal toxicity (MESH:D012164), abdominal discomfort (MESH:D000007), myocardial infarction (MESH:D009203), abdominal pain (MESH:D015746), autoimmune diseases (MESH:D001327), rheumatoid arthritis (MESH:D001172), lupus nephritis (MESH:D008181), toxicity (MESH:D064420), CKD (MESH:D051436), FSGS (MESH:D005923), IgA type nephritis (MESH:D009393), glomerulonephritides IgA (MESH:D005921), desquamation (MESH:D017490), nausea (MESH:D009325), Blurred vision (MESH:D014786), rheumatological conditions (MESH:D020763), thrombosis (MESH:D013927), diabetes (MESH:D003920), nephrotic syndrome (MESH:D009404), Berger's disease (MESH:D005922), Glomerular diseases (MESH:D007674)
- **Chemicals:** HCQ (MESH:D006886), chloroquine (MESH:D002738), rituximab (MESH:D000069283), Tacrolimus (MESH:D016559), Cyclosporine A (MESH:D016572), Mycophenolate mofetil (MESH:D009173), Leflunomide (MESH:D000077339), losartan (MESH:D019808), creatinine (MESH:D003404), Cyclophosphamide (MESH:D003520), 4-aminoquinolone (-), calcium (MESH:D002118), melanin (MESH:D008543)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12323010/full.md

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Source: https://tomesphere.com/paper/PMC12323010